The long-range goal of this project is to learn how essential fatty acids (EFA) act in metabolic regulations, with special emphasis on whether EFA could act in regulating fatty acid synthesis by influencing hormone action through alterations in the composition of membrane phospholipids, especially the plasma membrane. EFA depletion, either in the EFA-deficient rat or in the rat in which the liver is EFA-depleted because of refeeding a high carbohydrate diet after fasting, results in elevated levels of the so-called "lipogenic enzymes", including glucose-6-phosphate dehydrogenase (G6PDH) and the fatty acid synthetase complex (FAS). EFA could act in regulation of fatty acid synthesis through their role as prostaglandin precursors, through acting as inhibitors of enzymes involved in fatty acid synthesis, through acting as part or repressor molecules which repress the genes for the so-called "lipogenic enzymes," or through influencing action of hormones (which function in regulation of lipogenesis) by altering membrane lipids, especially phospholipids, required for function of hormonally-controlled enzymes. We have shown that the effect of EFA in reducing activities of "lipogenic enzymes" in liver of EFA-deficient rats or rats refed high carbohydrate diets after fasting is not due to reduced food or carbohydrate intake. Our approach is to investigate effects of EFA deficiency on composition and enzymatic activities of liver plasma membranes, especially enzymes which are hormonally controlled. Liver plasma membranes have been prepared by a sucrose-gradient method or a 2-phase polymer method, which is more rapid but gives results similar to the sucrose-gradient method. Increased NaK(Mg) - ATPase activity has been found in brain synaptosomes of EFA-deficient mice and in liver plasma membranes of EFA-deficient rats. NaK(Mg) - ATPase requires phosphatidyl serine (PS) for activity, and activation by PS is affected by the fatty acid composition of the added PS.